Preferential use of the VH5-51 gene segment by the human immune response to code for antibodies against the V3 domain of HIV-1.
Human anti-V3 monoclonal antibodies (mAbs) generated from HIV-1 infected individuals display diversity in the range of their cross-neutralization that may be related to their immunogenetic background. The study of the immunoglobulin (Ig) variable region gene usage of heavy chains have shown a preferential usage of the VH5-51 gene segment which was detected in 35% of 51 human anti-V3 mAbs. In contrast, human mAbs against other envelope regions of HIV-1 (anti-Env), including the CD4-binding domain, the CD4-induced epitope, and gp41 preferentially used the VH1-69 gene segment, and none of them used the VH5-51 gene. Furthermore, the usage of the VH4 family by anti-V3 mAbs was restricted to only one gene segment, VH4-59, while the VH3 gene family was used at a significantly lower frequency by all of the analyzed anti-HIV-1 mAbs. Multivariate analysis showed that usage of VH gene segments was significantly different between anti-V3 and anti-Env mAbs, and compared to antibodies from healthy subjects. In addition, the anti-V3 mAbs preferentially used the JH3 and D2-15 gene segments. The preferential usage of selected Ig gene segments and the characteristic pattern of Ig gene usage by anti-V3 mAbs can be related to the conserved structure of the V3 region.
Gorny
Miroslaw K
MK
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. mirek@gorny@med.nyu.edu
Wang
Xiao-Hong
XH
Williams
Constance
C
Volsky
Barbara
B
Revesz
Kathy
K
Witover
Bradley
B
Burda
Sherri
S
Urbanski
Mateusz
M
Nyambi
Phillipe
P
Krachmarov
Chavdar
C
Pinter
Abraham
A
Zolla-Pazner
Susan
S
Nadas
Arthur
A
D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D000914:Antibodies, Viral / Q000235:genetics* / Q000276:immunology; D000918:Antibody Specificity / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D015700:HIV Envelope Protein gp41; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D007135:Immunoglobulin Variable Region; C514787:gp41 protein, Human immunodeficiency virus 1